3-(amino-methylene)-5-phenyl-1,4-benzodiazepin-2-ones

ABSTRACT

Compounds of the formula   WHEREIN R1 and R2, which may be identical to or different from each other, are each hydrogen cycloalkyl, phenyl, -A-Y where A is alkyl of 1 to 5 carbon atoms or alkenyl of 1 to 5 carbon atoms, and Y is furyl, dialkylamino, hydroxyl, carbalkoxy or carbamido, OR, TOGETHER WITH EACH OTHER AND THE NITROGEN ATOM TO WHICH THEY ARE ATTACHED, PYRROLIDINO, PIPERIDINO, HEXAMETHYLENEIMINO, MORPHOLINO, THIOMORPHOLINO, THIOMORPHOLINO-S-oxide or N&#39;&#39;-alkylpiperazino, R3 is halogen, nitro or trifluoromethyl, R4 is hydrogen, halogen or trifluoromethyl, and R5 is hydrogen, alkyl, cycloalkyl-methyl, alkyl-amino-alkyl, dialkylamino-alkyl or trifluoro-methyl-alkyl; THE COMPOUNDS ARE USEFUL AS SEDATIVES, TRANQUILIZERS, MUSCLERELAXANTS AND ANTICONVULSIVES.

Unite States Pieper et al.

atent r191 [451 Mar. 18, 1975 l 3-( AMINO-M ETHYLENE )-5-PHENYL-l.4-

BENZODIAZEPIN-Z-ONES [73] Assignee: Boehringer Ingelheim GmbH,

lngelheim am Rhein, Germany Filed: July 5, 1973 [21] Appl. No.: 376,378

[30] Foreign Application Priority Data July 12, 1972 Germany 2234150 May 15, 1973 Germany 2324962 [52] US. Cl 260/2393 D, 424/244, 424/246,

424/248, 424/250, 424/267, 424/274 [51] Int. Cl C07d 53/06 [58] Field of Search 260/2407, 239.3 D

[56] References Cited OTHER PUBLICATIONS Usui et al., Takeda Kenkyusho Ho, I970, pages 145 to 145 (Japan), abstracted in Chemical Abstracts, Vol. 73, No. l48l9t, (1970) Primary Examiner-John D. Randolph [57] ABSTRACT Compounds of the formula I c cH-at 1 R 3 wherein R and R which may be identical to or different from each other, are each hydrogen cycloalkyl, phenyl, A-Y

where A is alkyl of 1 to'5 carbon atoms or alkenyl of l to 5 carbon atoms, and

Y is furyl, dialkylamino, hydroxyl, carbalkoxy or carbamido,

or, together with each other and the nitrogen atom to which they are attached, pyrrolidino, piperidino, hexamethyleneimino, morpholino, thiomorpholino, thiomorpholino-S-oxide or N-alkyl-piperazino,

R is halogen, nitro or trifluoromethyl,

R is hydrogen, halogen or trifluoromethyl, and

R is hydrogen, alkyl, cycloalkyl-methyl, alkyl-amino-alkyl, dialkylamino-alkyl or trifluoro-methyl-alkyl;

the compounds are useful as sedatives, tranquilizers. muscle-relaxants and anticonvulsives.

10 Claims, N0 Drawings 1 3-(AMINO-METHYLENE)-5-PHENYL-l,4-

BENZODIAZEPIN-Z-ONES This invention relates to novel 3-(amino-methylene)- -phenyl-l ,4-benzodiazepin-2-ones, as well as to methods of preparing these compounds.

More particularly, the present invention relates to a novel class of compounds represented by the formula wherein R, and R which may be identical to or different from each other, are each hydrogen, cycloalkyl, phenyl, -AY

where A is alkyl of l to 5 carbon atoms or alkenyl of l to 5 carbon atoms, and Y is furyl, dialkylamino, hydroxyl, carbalkoxy or carbamido, or, together with each other and the nitrogen atom to which they are attached, pyrrolidino, piperidino, hexamethyleneimino, morpholino, thiomorpholino, thiomorpholino-S-oxide or N'-lower alkyl-piperazino,

R is halogen, nitro or trifluoromethyl, R is hydrogen, halogen or trifluoromethyl, and R is hydrogen, lower alkyl, cycloalkyl-methyl, lower alkylamino-lower alkyl, di-lower alkyl-amino-lower alkyl or trifluoro-methyl-lower alkyl. The compounds embraced by formula I may be prepared by the following methods, inter alia: Method A For the preparation of a compound of the formula l wherein A, R R and R have the same meanings as in formula I, R, and R have the same meanings as in formula l except thiomorpholino-S-oxide, and except hydrogen, and Y has the same meanings as in formula 1 except hydroxyl, carbalkoxy and carbamido, by reacting a S-phenyl-l,4-benzodiazepin-2-one of the formula wherein R3, R and R have the meanings previously defined, with a formamidc-acetal of the formula R6O/CH N\R2' wherein R, and R which may be identical to or different from each other, are each cycloalkyl, phenyl, -AY

where A has the same meanings as'in formula I, and

Y is furyl or di(lower alkyl)amino, or, together with each other and the nitrogen atom to which they are attached, pyrrolidino, piperidino, hexamethyleneimino, morpholino, thiomorpholino or N'- lower alkyl-piperazino, and

R is lower alkyl.

The reaction is advantageously carried out under exclusion of moisture and in a solvent medium at a temperature between 20 and 160c, preferably between and C. Examples of suitable solvent media are inert solvents, such as tetrahydrofuran, dioxane or dimethylformamide, or preferably, however, a sufficient excess of the formamide-acetal of the formula Ill over and above the stoichiometrically required amount. The reaction will also proceed in the absence of a solvent medium.

Method B By reacting a compound of the formula wherein R5,, R and R have the same meanings as in formula I, and R and R which may be identical to or different from each other, are each optionally substituted alkyl, optionally substituted aryl or, together with each other and the nitrogen atom to which they are attached, form a heterocyclic ring, but preferably alkyl of l to 3 carbon atoms, with an amine of the formula wherein R, and R have the same meanings as in formula l.

The reaction is advantageously performed under exclusion of moisture in a solvent medium, and optionally in the presence of a catalytic amount of an acid addition salt, such as the hydrochloride, of the amine of the formula V, at a temperature between 50 and C, preferably between 80 and 140C. Examples of suitable solvent media are inert organic solvents, such as tetrahydrofuran, dioxane or dimethylformamide, or a sufficient excess of the amine of the formula V over and above the stoichiometrically required amount. The reaction may, however, also be performed without a solvent medium. Method C In those instances where method A or B yields as an end product a compound of the formula I wherein R is hydrogen and R and R do not contain a reactive hydrogen atom, such a compound can be alkylated in the 1-position by reacting it with a substituted alkyl halide of the formula Hal R wherein R has the same meanings as R in formula 1 except hydrogen, and

Hal is chlorine, bromine or iodine, preferably in the presence of a strong base, such as sodium hydride or sodium methylate, in an inert solvent such as dimethylformamide, and advantageously at room temperature.

A starting compound of the formula 11 may be obtained by known methods, such as by reacting a correspondingly substituted Z-amino-benzophenone with a haloacetic acid halide, followed by cyclization of the intermediate with ammonia. If a compound of the formula 11 wherein R is hydrogen is obtained in this manner, the same may be converted into the corresponding compound wherein R, has the other meanings defined above by reaction with an alkyl halide of the formula VI [see Chem. Reviews 86, 747785 (1968); and J. Pharm. Sci. 53, 577-590 (1969)].

A starting compound of the formula 1V may be obtained by reacting a corresponding 1,3-dihydro-1,4- benzodiazepin2-one with a corresponding formamideacetal in analogy to method A.

The following examples further illustrate the present invention and will enable others skilled in the art to un derstand it more completely. It should be understood, however, that the invention is not limited solely to the particular examples given below,

EXAMPLE 1 7-Chloro-5-(2-chloro-phenyl)-1,3-dihydro-3- (dimethylaminomethylene)-1 -methyl-2H-l ,4-

benzodiazepin-Z-one by method A A suspension of 55 gm of 7-ch1oro-5-(2-chlorophenyl)-l,3-dihydro-1-methyl-2H-1,4-benzodiazepin- 2-one in 85 ml of N,N-dimethyl-formamide diethylacetal was heated to 130C in a vessel equipped with a descending condenser, whereby a clear solution was formed after a short time. The temperature of the reaction solution was maintained at 130C for 41 hours, during which time the ethanol formed by the reaction slowly distilled over. Thereafter, the reaction solution was cooled to about 80C and then admixed with 50 ml of isopropanol. Upon further cooling of the mixture, a reddish-orange crystalline substance separated out which was collected by vacuum filtration, washed with petroleum ether and recrystallized from isopropanol, whereupon it had a.melting point of 202203C. It was identified to be the compound of the formula EXAMPLE 2 7-Chloro-5-(2'-chloro-phenyl)-l ,3-dihydro-3- (dimethylaminomethylene )-2H 1 ,4-benzodiazepin- 2-one by method A i A suspension of 50 gm of 7-chloro-5-(2-chlorophenyl)l ,3-dihydro-2H-1,4-benz0diazepin-2-onc in ml of N,N-dimethyl-formamidc dicthylacctal was heated to C in a vessel equipped with a descending condenser, whereby a clear solution was formed after a short time. The temperature of the reaction solution was maintained at 130C for 40 minutes, during which time the ethanol formed by the reaction slowly distilled over. Thereafter, the reaction solution was allowed to cool, and the red precipitate was collected by vacuum filtration, washed with petroleum ether and recrystallized from methanol, whereupon it had a melting point of 23924lC. It was identified to be the compound of the formula EXAMPLE 3 which had a melting point of 2l3215C,

EXAMPLE 4 7Chloro-5-(2'-chloro-phenyl)-1,3-dihydro-3- (dimethylaminomethylene)- l -methyl-2H-1 ,4- benzodiazepin-2-one by method C 35.6 gm ofa methanolic 30% sodium methylate solution were added dropwise to a solution of 46.5 gm of 7-chloro-5-(2-chloro-phenyl)-l ,3-dihydro-3- (dimethylamino-methylene)-2H-l ,4-benzodiazepin- 2-one in 300 ml of dry dimethylformamide at room temperature, accompanied by stirring, and the result ing mixture was stirred for minutes more at room temperature and subsequently cooled to +5C while stirring. Then, while maintaining that temperature by cooling, 58 gm of methyl iodide were added at a slow dropwise rate, again while stirring, and the resulting mixture was stirred for 90 minutes more at +5C. Thereafter, the yellow precipitate which had formed was collected by vacuum filtration, washed with much water, dried and recrystallized from isopropanol, yielding the compound named in the heading above, which had a melting point of l99200C.

EXAMPLE 5 7-Bromo-5-( 2-chloro-phenyl )-l ,3dihydro- 1 -methyl- 3-[N-methyl-N-(morpholinocarbonyl-methyl)-aminomethylene]-2H'l,4-benzodiazepin-2-one by method A A suspension of 8.4 gm of 7-bromo-5(2-chlorophenyl)-l ,3-dihydro-3(dimethylamino-methylene)-imethyl-Zl-ll ,4-benzodiazepin-2-one in gm of sarcosine morpholide was heated to 160C, while stirring, whereby a clear solution was formed after some time, which was stirred for 90 minutes more at 160C. Thereafter, the reaction mixture was allowed to cool and was then taken up in a mixture consisting of 150 ml each of tetrahydrofuran and ether. The resulting solution was washed three times with 100 ml of water each, and the organic phase was dried over magnesium sulfate and evaporated in vacuo. The residue was purified on a silicagel column, using a l91l-mixturc of chloroform and methanol as the flow agent. Those fractions containing the desired compound were combined, the solvent mixture was distilled off in vacuo, and the residue was recrystallized from tetrahydrofuran, yielding the compound of the formula which had a melting point of 200-202C.

EXAMPLE 6 Using a procedure analogous to that described in Example 2, 3-(dimethylamino-methylene)-5-phenyl-7- chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one, m.p. 237-240C, of the formula was prepared from 5-phenyl-7-chlo ro-l ,3-dihydro-2H- 1,4-benzodiazepin-2-one and N,N-dimethylformamide-diethylacetal.

EXAMPLE 7 Using a procedure analogous to that described in Example l, l-methyl-3-(dimethylamino-mcthylene)-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4benzodiazepin- Z-onc, m.p. 2042()5C, was prepared from l-methyl 5-phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and N,N-dimethylformamide-diethylacetal.

EXAMPLE 8 EXAMPLE 9 Using a procedure analogous to that described in Example 2, 3-(diethylamino-methylene)-5-phenyl7- chloro-l ,3-dihydro-2H- l ,4-benzodiazepin-2-one, m.p. 236-238C, was prepared from 5-phenyl-7-chloro-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-one and N,N-diethylformamide-diethylacetal.

EXAMPLE l0 Using a procedure analogous to that described in Example l, l-methyl-3-(diethylamino-methylene)-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-0ne, m.p. l92-l94 C, was preparedfrom l-rnethyl- 5phenyl-7-chlorol ,3-dihydro-2H- l ,4-benzodiazepin- 2-one and N,N-diethyl-formamide-diethylacetal.

EXAMPLE I 1 Using a procedure analogous to that described in Exvample 2, 3-(di-n-propylamino-methylene)-5-phenyl-7- chloro-l ,3-dihydro-2H 1 ,4-benzodiazepin-2-one, m.p. 200-201C, was prepared from 5-phenyl-7-chloro- 1 ,3-dihydro-Zkl-l ,flbenzodiazepin z one and N ,N- di-n-propyl-formamide-diethylacetal.

EXAMPLE 12 Using a procedure analogous to that described in Example l, l-mcthyl-3-(di-n-propylaminn-methylene)-5- phcnyl-7-chlorol ,3-dihydro-2H'l ,4-benzodiazepin- 2-one, m.p. l34-l35C, was prepared from l-methyl- 5-phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and N,N-di-n-propyl-formamide-diethylacetal.

EXAMPLE 13 Using a procedure analogous to that described in Example 2, 3-(diallylamino-methylene)-5-phenyl-7- chloro-l ,3-dihydro-2H- l ,4-benzodiazepin-2-one, m.p. l73l75C, of the formula cacao \QHQPCHIECHQ was prepared from -phenyl-7 -chloro-l ,3-dihydro-2H- 1,4-benzodiazepin-2-one and N,N-diallyl-formamidediethylacetal.

EXAMPLE 14 Using a procedure analogous to that described in Example 2, 3-(di-n-butylamino-methylene)-5-phenyl-7- chloro-1,3-dihydro-2H-l,4-benzodiazepin-2-one, m.p. l38l40C, was prepared from 5-phenyl-7-chloro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and N,N-di-nbutyl-formamide-diethylacetal.

EXAMPLE Using a procedure analogous to that described in Example 1, l-methyl-3-(di-n-butylamino-methylene)-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 9597C, was prepared from l-methyI-S- phenyl-7-chlorol ,3-dihydro-2H- l ,4-benzodiazepin- 2-one and N,N-di-n-butyl-formamide-diethylacetal.

EXAMPLE 16 Using a procedure analogous to that described in Example 2, 3-(diisopropylamino-methylene)-5-phenyl-7- chloro-l,3-dihydro-2H-1,4-benzodiazepin-2-one, m.p. 248250C, was prepared from 5-phenyl-7-chloro-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-one and N,N- diisopropyl-formamide-diethylacetal.

EXAMPLE 17 Using a procedure analogous to that described in Example l, l-methyl-3-(diisopropylamino-methylene)-5- phenyl-7-chloro-l ,S-dihydro-ZH-l ,4-benzodiazepin- 2-0ne, an amorphous foam (proof of structure by IR-, UV- and NMR-spectra), was prepared from l-methyl- 5-phenyl-7-chloro-1,3-dihydro-2H-l ,4-benzodiazepin- 2-one and N,N-diisopropyl-formamide-diethylacetal.

EXAMPLE 18 Using a procedure analogous to that described in Example 2, 3-[(N-cyclohexyl-N-methyl-amino)- methylene]-5-phenyl-7-chloro-l ,3-dihydro-2-H-1,4- benzodiazepin-2-one, m.p. 247250C, of the formula was prepared from 5-phenyl-7-chloro-l ,3-dihydro-2H- l,4-benzodiazepin-2-one and (Ncyclohexyl-N-methylformamide)-diethylacetal.

EXAMPLE 19 Using a procedure analogous to that described in Example l, l-methyl-B-l (N-eyclohexyl-l l-methyl-amino)- methylene I-S-phenyl-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one. m.p. l67l(1)C, was prepared from l-methyl-5-phenyl-7-chlorol 3-dihydro-2H-l ,4- benzodiazepin-Z-one and (N-cyclohexyl-N-methylformamide)-dicthylacetal.

EXAMPLE 20 Using a procedure analogous to that described in Example 2, 3-(pyrrolidino-methylene)-5-phcnyl-7- chlorol ,3-dihydro-2H- l ,4-benzodiazepin-2-one, m.p. 252254C, of the formula was prepared from 5-phenyl-7-chlor0-l,3-dihydro-2H- l,4-benzodiazepin-2-one and pyrrolidino-diethoxymethane.

EXAMPLE 21 Using a procedure analogous to that described in Example 1, l-methyl-3-(pyrrolidino-methylene )-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 184186C, was prepared from l-methyl- 5-phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and pyrrolidino-diethoxy-methane.

EXAMPLE 22 Using a procedure analogous to that described in Example 2, 3-(piperidino-methylene)-5-phenyl-7-chloro- 35 1,3-dihydro-2H-l,4-benzodiazepin-2-one, m.p.

242243C, of the formula was prepared from l-methyl-5-phenyl-7-chloro-l,3- dihydro-ZH-l,4-benzodiazepin-2-one and piperidinodiethoxy-methane.

EXAMPLE 23 phenyl-7-chlorol .3-dihydro-2H-l ,4-benzodiazepin- 2-0ne, m.p. 248250C, of the formula ample was prepared from -phenyl-7-chloro-l,3-dihydro-2H- 1,4-benzodiazepin-2-one and hexamethyleneiminodiethoxy-methane.

EXAMPLE Using a procedure analogous to that described in Example 1, l-methyl-3-(hexamethyleneiminomethylene )-5-phenyl-7-chlorol ,3- dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l96l98C, was prepared from l-methyl-5-phenyl-7-chlor0-1,3-dihydro-2H-l,4- benzodiazepin-Z-one and hexamethyleneiminodiethoxy-methane.

EXAMPLE 26 Using a procedure analogous to that described in Example 2, 3-(morpholino-methylene)-5-phenyl-7- -chlorol ,3-dihydro-2H- l ,4-benzodiazepin-2-one, m.p. 251252C (decomp), of the formula was prepared from 5-phenyl-7-chloro-l,3-dihydro-2H- l,4-benzodiazepin-2-one and morpholino-diethoxymethane.

EXAMPLE 27 Using a procedure analogous to that described in EX- ample l, 1-methyl-3-(morpholino-methylene)-5- phenyl-7-chlorol ,3-dihydro-2l-l-l ,4-benzodiazepin- 2-one, m.p. 169l71C, was prepared from l-methyl- 5-phenyl-7-chloro-l,3-dihydro-2H-1,4-benzodiazepin- 2-one and morpholino-diethoxy-methane.

EXAMPLE 28 Using a procedure analogous to that described in Ex- I, 1-methyl-3-[(N"methyl-piperazinomethylene]-5-phenyl-7-chloro-l ,3-dihydro-2H- 1 ,4-

benzodiazepin-Z-one, m.p. 14l-l43C, of the formula M was prepared from l-methyl-5-phenyl-7-chloro-l,3- dihydro-2l-l-l,4-benzodiazepin-2-one and (N-m'ethylpiperazino)-diethoxy-methane.

EXAMPLE 29 Using a procedure analogous to that described in Example l, 1-methyl-3-[ (N-methyl-N-ethylamino methylene]-5-(2 -chloro-phenyl )-7-chloro-l ,3- dihydro-ZH- l ,4-benzodiazepin-2-one, m.p. 8891C,

was prepared from l-methyl-5-(2'-chloro-phenyl)-7- chloro-l,3-dihydro-2H-1,4-benzodiazepin-2-one (N-methyl-N-ethyl-formamide )-diethylacetal.

and

EXAMPLE 30 Using a procedure analogous to that described in EX- ample 2, 3-(diethylamino-methylene)-5-(2'-chlorophenyl)-7-chloro-l ,3-dihydro-2H- l ,4-benz0diazepin- 2-one, m p. 204-206C, was prepared from 5-(2'- chloro-phenyl)-7-chloro-l ,3-dihydro-2-H-l ,4- benzodiazepin-Z-one and N,N-diethyl-formamide diethylacetal.

EXAMPLE 31 Using a procedure analogous to that described in Example 2, 3-(di-npropylamino-methylene)-5-(2'- chloro-phenyl )-7-chloro-l ,3-dihydro-2H- l ,4- benzodiazepin-Z-one, m.p. 226227C, was prepared from 5-(2-chloro-phenyl)-7-chloro-1,3-dihydro-2-H- 1,4-benzodiazepin-2-one and N,N-dinpropylformamide-diethylacetal.

EXA M PLE 32 Using a procedure analogous to that described in Example 2, 3-(diallylamino-methylene)-5-(2-chlorophenyl)-7-chloro-l ,3-dihydro-2-H-1,4-benzodiazepin- 2-one, m.p. l67C, was prepared from 5-(2'- chloro-phenyl)-7-chloro-l ,3-dihydro-2H-1,4- benzodiazepin-Z-one and N,N-diallyl-formamide diethylacetal.

EXAMPLE 33 Using a procedure analogous to that described in Example 2, 3-(di-nbutylamino-methylene)-5-(2-chl0rophenyl) -7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- Z-one, m.p. 2ll2l3C, was prepared from 5-(2'- chloro-phenyl)-7-chloro-l ,3-dihydro-2H- l ,4- benzodiazepin-Z-one and N,N-di-n-butyl-formamidediethylacetal.

EXAMPLE 34 Using a procedure analogous to that described in Example 2, 3-(diisopropylamino-methylene)-5-(2- chloro-phenyl)-7-chlor0-1,3-dihydro-2H-l,4- benzodiazepin-Z-one, m.p. 222224C, was prepared from 5-(2-chloro-phenyl)-7-chloro-l,3-dihydro-2H- 1,4-benzodiazepin-2-one and N,N- diisopropylformamide-diethylacetal.

EXAMPLE 35 Using a procedure analogous to that described in Example 2, 3-[(N-B-dimethylamino-ethyl-N-methylamino)-methylene]-5-(2-chloro-phenyl)7-chlorol,3-dihydro-2H- l ,4-benzodiazepin2-one, m.p. 202205C. of the formula was prepared from -(2-chloro-phenyl)-7-chloro-l,3-

dihydro-ZH- l ,4-benzodiazepin-2-one and [N(B- dimethylamino-ethyl)-N-methyl-formamide]- diethylacetal.

EXAMPLE 36 Using a procedure analogous to that described in Example l, l-methyl-3-[(N-B-dimethylamino-ethyl-N- methylamino)-methylene]-5-(2-chloro-phenyl)-7- chloro-l ,3-dihydro-2l-ll ,4-benzodiazepin-2-one, m.p. l30l 32C, was prepared from l-methyl-5-(2-chlorophenyl )-7-chloro-l ,3-dihydro-2H- 1 ,4-benzodiazepin- 2-one and- [N-(B-dimethylamino-ethyl)-N-methylformamide]-diethylacetal.

EXAMPLE 37 Using a procedure analogous to that described in Example l, 1-methyl-3-[(N-methyl-anilino)-methylene]- 5-( 2 '-chloro-phenyl)-7-chlorol ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l97-l99C, of the formula was prepared from l-methyl-5-(2-chloro-phenyl)-7- chlorol ,3-dihydro-2H- l ,4-benzodiazepin-2-one and (N-methyl-anilino)-diethoxy-methane.

EXAMPLE 38 Using a procedure analogous to that described in Example 2, 3-[(N-cyclohexyl-N-methyl amino)- methylene]-5-(2'-chloro-phenyl)-7-chloro-1,3- dihydro-Zl-I- l ,4-benzodiazepin -2-one, m .p. l97200C, was prepared from 5-(2'-chloro-phenyl)- 7-chlorol ,3-dihydro-2-H-l ,4-benzodiazepin-2-one and (N-cyclohexyl-N-methyl-formamide)- diethylacetal.

EXAMPLE 39 Using a procedure analogous to that described in Ex-- ample 2, 3-(pyrrolidino-methylene)-5-(2-chl0rophenyl )-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 247249C, was prepared from 5-(2- chloro-phenyl)-7-chloro-1,3-dihydro-2H-l ,4- benzodiazepin-Z-one and pyrrolidinodiethoxymethane.

I v m /CH2-CH2-N(CH3)2 phenyl )-7-chloro-l ,3-dihydro-2H- l ,4-benzodiazepin- 2-one, m.p. 245248C (decomp), was prepared from 5-( 2 -chloro-phenyl)-7-chlorol ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and piperidino-diethoxymethane.

EXAMPLE 4] Using a procedure analogous to that described in Example 2, 3-(hexamethyleneimino-methylene)-5-(2'- chlorophenyl)-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 238239C, was prepared from 5-(2-chloro-phenyl)-7-chloro-l,3-dihydro-2H- l,4-benzodiazepin-2-one and hexamethyleneiminodiethoxy-methane.

EXAMPLE 42 Using a procedure analogous to that described in Example 2, 3-(morpholino-methylene)-5-(2-chlorophenyl)-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 209-2l 1C, was prepared from 5-(2'- chloro-phenyl)-7-chlorol ,3-dihydro2H-l ,4- benzodiazepin-2-one and morpholino-diethoxymethane.

EXAMPLE 43 Using a procedure analogous to that described in Example l, l-methyl-3-(morpholino-methylene)-5-(2- chlorophenyl)-7-chloro-l ,3-dihydro-2Hl ,4- benzodiazepin-2'one, m.p. l58l60"C, was prepared from l-methyl-5-( 2 -chlorophenyl)-7-chloro-l ,3- dihydro-ZH-l,4benzodiazepin-2-one and morpholinodiethoxy-methane.

EXAMPLE 44 Using a procedure analogous to that described in Example l, l-(cyclopropyl-methyl )-3-(morpholinomethylene)-5-(2'-chloro-phenyl)-7-chloro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one, an amorphous foam, of the formula (proof of structure by lR-, UV- and NMR-spectra) was prepared from l-(cyclopropyl-methyl)-5-(2-chlorophenyl )-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and morpholino-diethoxy-methane.

EXAMPLE 45 Using a procedure analogous -to that described in Example 2, 3-[(N'-methyl-piperazino)-methylene]-5-(2- chlorophenyl)-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l94-l96C, was prepared from 5-(2-chloro-phenyl)-7-chloro-l,3-dihydro-2H- l,4benzodiazepin-2-one and (N-methyl-piperazino)- diethoxy-methane.

EXAMPLE 46 Using a procedure analogous to that described in Example l l-methyl-3-[(N-methyl-piperazino)- methylene ]-5-( 2"chloro-phenyl)-7-chloro-l ,3- dihydro2H-l,4-benz0diazepin-2-one, an amorphous foam (proof of structure by IR-, UV- and NMR- spectra), was prepared from l-methyl-5-(2-chlorophenyl)-7-chloro-l ,3dihydro-2H-l ,4-benzodiazepin- 2-one and (N-methyl-piperazino)-diethoxy-methane.

EXAMPLE 47 Using a procedure analogous to that described in Ex-' ample l, l-methyl-3-(dimethylamino-methylene)-5- (2'-fluorophenyl)-7-chlor0- l ,3-dihydro-2H-l ,4-

benzodiazepin-2-one, m.p. 157l59C, of the formula CH tic/ =cH-N c 1 was prepared from l-mcthyl-5-(2'-fluoro-phenyl)-7- chlorol ,3-dihydr-2H-l ,4-benzodiazepin-2-one and N,N-dimethyl-formamide-diethylacetal.

EXAMPLE 48 Using a procedure analogous to that described in Example l, l-methyl-3-(morpholino-methylene)-5-(2- fluorophenyl)-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 172l74C, was prepared from l-methyl--( 2 '-fluoro-phenyl) 7-chloro-l ,3- dihydro-2H-l,4-benZ0diazepin-2-one and morpholinodiethoxy-methane.

EXAMPLE 49 Using a procedure analaogous to that described in Example 2, 3-(dimethylamino-methylene)-5-(2'- chloro-phenyl)-7-bromo-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 200223C, was prepared from 5-(2'-chloro-phenyl)-7-bromo-l,3-dihydro-2H- l,4-bcnzodiazepin-2-one and N,N-dimethyl-formamide -cliethylacetal.

EXAMPLE 50 Using a procedure analogous to that described in Example l-methyl-3-(diethylamino-methylene)-5-(2'- chlorophenyl)-7-bromo-l ,3-dihydro-2-H- l ,4-

benzodiazepin-Z-one, m.p. l3ll33C, was prepared from l-methyl5-( 2'-chloro-phenyl)-7-bromo-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and N.N-diethylformamide-diethylacetal.

EXAMPLE 51 Using a procedure analogous to that described in Example l, l-methyl-3-(piperidino-methylene )-5-( 2- chlorophenyl )-7-bromo-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l76-l78C, was prepared from l-methyl-5-(2'-chloro-phenyl)-7-bromo-l ,3-

dihydro-ZH-l,4-benzodiazepin-2-one and piperidinodiethoxy-methane.

EXAMPLE 52 Using a procedure analogous to that described in Example l, l-methyl-3-(hexamethyleneiminomethylene)-5-( 2-chloro-phenyl)-7-bromo-l ,3- dihydro-l,4-benzodiazepin-2-one, m.p. ll42C, was prepared from l-methyl-5-(2-chloro-phenyl)-7- bromo-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and hexamethyleneimino-diethoxy-methane.

EXAMPLE 53 Using a procedure analogous to that described in Example 1, l-methyl-3-(morpholino-methylene)-5-(2'- chlorophenyl)-7-bromo-l ,3-dihydro-2H-l ,4 benzodiazepin-Z-one, m.p. l48-l53C, was prepared from l-methyl-5(2-chloro-phenyl)-7-bromo-l ,3- dihydro-2H-l ,4-benzodiazepin-2-one and morpholinodiethoxy-methane.

EXAMPLE 54 Using a procedure analogous to that described in Example l, l-methyl-3-(dimethylamino-methylene)-5- (2 '-fluorophenyl )-7-bromo-l ,3-dihydro-2H-l ,4- benzocliazepin-2-one, m.p. l72-l73C, was prepared from l-methyl-5-( 2 -fluoro-phenyl )-7-bromo-l ,3- dihydro-ZH-l ,4-bcnzodiuzepin-2-one and Nb]- dimethyl-formamide-diethylacetal.

EXAMPLE 55 Using a procedure analogous to that described in EX- was prepared from 5-phenyl-7-nitro-l,3-dihydro-2H- 1 ,4-benzodiazepin-2-one and N,N-dimethylformamide-diethylacetal.

EXAMPLE 56 Using a procedure analogous to that described in Example l, l-methyl-3-(dimethylamino-methylene)-5- phenyl-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 228.5229.5C, was prepared from 1- methyl-5-phenyl-7-nitrol ,3-dihydro-2H-l ,4-

benzodiazepin-Z-one and N,N-dimethyl-formamidediethylacetal.

EXAMPLE 57 Using a procedure analogous to that described in Example 2, 3-(diallylamino-methylene)-5-phenyl-7-nitro- 1,3-dihydro-2H-l ,4-benzodiazepin-2-one, m.p. l94l95C, was prepared from -phenyl-7-nitro-l,3- dihydro-ZH-l,4-benzodiazepin-2-one and N,N-diallylformamide-diethylacetal.

EXAMPLE 58 Using a procedure analogous to that described in Example l, 3-[N-(B-dimethylamino-ethyl)-N-methylaminomethylene]-5-phenyl-7-nitro-l ,3-dihydro-2H- 1,4-benzodiazepin-2-one, m.p. 200202C, was prepared from 5-phenyl-7-nitro-l,3-dihydro-2H-l,4- benzodiazepin-2-one and [N-(B-dimethylamino-ethyl)- N-methyl-formamide]-diethylacetal.

EXAMPLE 59 Using a procedure analogous to that described in Example 2, 3-(morpholino-methylene)-5-phenyl-7-nitrol ,3dihydro-2H-1,4-benzodiazepin-2-one, mop. 243-245C (decomp.), was prepared from 5-phenyl-7- nitro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and morpholino-diethoxy-methane.

EXAMPLE 60 Using a procedure analogous to that described in Example 2, l-methyl-3-(morpholino-methlene)-5-phenyl- 7-nitrol ,3-dihydro-2-H-l ,4-benzodiazepin-2-one, mp. 21 l2l2C, was prepared from l-methyl-S- phenyl-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and morpholino-diethoxy-methane.

EXAMPLE 6] Using a procedure analogous to that described in Example 2, 3-(dimethylamino-methylene)-5-(2'-chlorophenyl )-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 24lC (decomp.); was prepared from 5- (2'-chloro-phenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one and N,N-dimethylformamide diethylacetal.

EXAMPLE 62 Using a procedure analogous to that described in Example 2, 3-(diethylamino-methylene)-5-(2-chlorophenyl)-7-nitro-l ,3-dihydro-2l-ll ,4-benzodiazepin- 2-one m.p. 208209C, was prepared from 5-(2- chloro-phenyl)-7-nitro-l ,3-dihydro-2H-1 ,4- benzodiazepin-Z-one and N,N-diethyl-formamidediethylacetal.

EXAMPLE 63 EXAMPLE 64 Using a procedure analogous to that described in Example 2, 3(di-n-propylamino-methylene )-5-( 2 chloro-phenyl )-7-nitrol ,3-dihydro-2H-l ,4 benzodiazepin-2-one, m.p. 24l242C, was prepared from 5-(2'-chloro-phenyl)-7-nitro-l ,3dihydro-2H-l ,4- benzodiazepin-Z-one and N,N-di-n-propylformamidediethylacetal.

EXAMPLE 65 Using a procedure analogous to that described in Ex,- ample l, l-methyl-3-(di-n-propylamino-methylene)-5- (2'-chloro-phenyl )-7nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 7l75C, was prepared from l-methyl-5-(2-chlorophenyl)-7-nitrol ,3 dihydro-ZH-l,4-benzodiazepin-2-one and N,Ndi-npropyl-formamide-diethylacetal.

EXAMPLE 66 Using a procedure analogous to that described in Example 2, 3-(diallylamino-methylene)-5-(2-chlorophenyl)-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. l79-l8lC, was prepared from 5-(2'- chloro-phenyl-)-7-nitrol ,3-dihydro-2H-l ,4- benzodiazepin-2-one and N,N-diallyl-formamidediethylacetal.

EXAMPLE 67 Using a procedure analogous to that described in Example l, l-methyl-3-(diallylamino-methylene)-5-(2'- chlorophenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 5560C, was prepared from l-methyl5-( 2-chloro-phenyl)-7-nitro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and N,N-diallylformamide-diethylacetal.

EXAMPLE 68 Using a procedure analogous to that described in Example 2, 3-(diisopropylaminc-methylene)-5-(2'- chloro-phenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 2l12l3C, was prepared from 5-( 2-chloro-phenyl)-7-nitro-l ,,3-dihydro-2H- l,4-benzodiazepin-2-one and N,N-diisopropylformamide-diethylacetal.

EXAMPLE 69 Using a procedure analogous to that described in Example l, l-methyl-3-(diisopropylamino-methylene)-5- (2-chloro-phenyl)-7-nitro-l,3-dihydro-2H-1,4' benzodiazepin-2-one, m.p. l56l58C, was prepared from l-methyl-5-(2-chlorophenyl)-7-nitro-l ,3- dihydro-2H-l ,4-benzodiazepin-2-one and N,N- diisopropyl-formamide-diethylacetal.

EXAMPLE 70 Using a procedure analogous to that described in Example 2, 3-[(N-cyclohexyl-N-methyl-amino)- methylene]-5-( 2'-chloro-phenyl)-7-nitrol ,3-dihydro- 2H-l ,4-benzodiazepin-2-one, m.p. 2092l 1C, was prepared from 5-(2'-chloro-phenyl)-7-nitro-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-one and (N- cyclohexyl-N-methyl-formamide)-diethylacetal.

EXAMPLE 7] Using a procedure analogous to that described in Example 1, l-methyl-3-[(N-cyclohexyl-N-methyl-amino)- methylene]-5(2'-chloro-phenyl )-7-nitro-l ,3-dihydro- 2H-l,4-benzodiazepin-2-one, m.p. l07lO9C, was prepared from l-methyl- -(2"-chloro-phenyl)-7-nitro- 1,3-dihydro-2H-1,4-benzodiazepin-2-one and (N- cyclohexyl-N-methyl-formamide)-diethylacetal.

EXAMPLE 72 Using a procedure analogous to that described in Example l, l-methyl-3-[(N-methyl-anilino)-methylene]- 5-( 2'-chlorophenyl)-7-nitro-l ,3-dihydro-2l-l-1 ,4- benzodiazepin-2-one, m.p. l83185C, was prepared from l -methyl-5-(2-chlorophenyl)-7-nitro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and (N-methyl- N-phenyl-formamide)-diethylacetal.

EXAMPLE 73 Using a procedure analogous to that described in Example 2, 3-(pyrrolidino-methylene)-5-(2'-chlorophenyl)-7-nitrol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. l252C, was prepared from 5-(2- chlorophenyl)-7-nitro-l,3-dihydro-2H-1,4- benzodiazepin-Z-one and pyrrolidino-diethoxymethane.

EXAMPLE 74 Using a procedure analogous to that described in Example l, l-methyl-3-(pyrrolidino-methylene )-5-( 2 chlorophenyl )-7-nitro-1 ,3-dihydro-2H- l ,4- benzodiazepin-2-one, m.p. l84l85C, was prepared from l-methyl-5-(2'chloro-phenyl)-7-nitro-1,3 dihydro-ZH-l,4-benzodiazepin-2-one and pyrrolidinodiethoxy-methane.

EXAMPLE 75 Using a procedure analogous to that described in Example l, l-methyl-3-(piperidino-methylene)5-(2'- chloro-phenyl )-7-nitrol ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. l39-l4lC., was prepared from l -methy|-5-( 2 '-chloro-phenyl )-7-nitro-l ,3- dihydro-2H-l,4-benzodiazepin-2-onc and piperidinodiethoxyrnethane.

EXAMPLE 76 Using a procedure analogous to that described in Example 2, 3-(piperidino-methylene )-5-(2'-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin- 2-one, m.p. 235236C., was prepared from 5-(2'- chloro-phenyl)-7-nitro-1 ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and piperidino-diethoxymethane.

EXAMPLE 77 Using a procedure analogous to that describedin Example 2, 3-(hexamethyleneimino-methylene)-5-(2'- chloro-phenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 2l72l8C, was prepared from 5-(2'-chloro-phenyl)-7-nitro-l,3-dihydro-2H-1,4- benzodiazepin-Z-one and hexamethylene-iminodiethoxy-methane.

EXAMPLE 78 Using a procedure analogous to that described in Example 2, 3-(morpholino-methylene)-S-(2'-chlorophenyl l-7-nitrol .3-dihydro-2H-l ,4-hcnzodiazcpinc- Z-onc, m.p. 24(1248C, was prepared from 5-(2'- chloro-phcnyl)-7-nitro-1,3-dihydro-2H-l ,4- benzodiazcpin-2-onc and morpholino-diethoiiymethane.

EXAMPLE 79 Using a procedure analogous to that described in Ex ample 2, 3-(dimethylamino-methylene)-5-(2'-fluorophenyl )-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 243244C (decomp.), was prepared from 5-(2-fluoro-phenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one and N,N-dimcthyl-formamidcdiethylacetal.

EXAMPLE 80 Using a procedure analogous to that described in Example 2, l-methyl-3-(dimethylamino-methylenc)-5- (2'-f1uoro-phenyl)-7-nitro-l ,3-dihydro-2H- l ,4- benzodiazepin-Z-one, m.p. l93-l94.5C, was prepared from l-methyl-5-(2-fluoro-phenyl)-7-nitro-l,3- dihydro-2H-l,4-benzodiazepin-2-one and, N,N-dimethyl-formamide-diethylacetal.

EXAMPLE 81 Using a procedure analogous to that described in Example 2, phenyl)-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 20l202C, was prepared from 5-(2'- fluoro-phenyl )-7-nitro-l ,3-dihydro-2H- l ,4- benzodiazepin-2-one and N,N-diallyl-formamidediethylacetal.

EXAMPLE 82 Using a procedure analogous to that described in Example 2, 3-(morpholino-methylene)-5-(2 -fluorophenyl)-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 246-249C (decomp.), was prepared from 5-(2-fluoro-phenyl)-7-nitro-l ,3-dihydro-2H- l ,4- benzodiazepin-2one and morpholino-di-ethoxy methane.

EXAMPLE 83 EXAMPLE 84 Using a procedure analogous to that described in Example 3, 3-(amino-methylene)-5-phenyl-7-chloro- 1,3- dihydro-2H- l ,4-benzodiazepine-2-one, m.p. 244247C, of the formula was prepared from 3-(dimethylaminn-methylene)-5- phenyl-7-chlorol ,3-dihydro-2Hl ,4-benzodiazepin- 2-one and ammonia.

3-(diallylamino-methylene )-5-( 2-fluorochloro-l,3-dihydro-2H-1,4-benzodiazepin-2-one and ammonia.

EXAMPLE 86 Using a procedure analogous to that described in Example 3, 3-(methylamino-methylene)-5-phenyl-7- chloro-l ,3-dihydro-2H- l ,4-benzodiazepin-2-one, mp. 210C, of the formula cf rat was prepared from 3-(dimethylamino-methylene)-5-, phenyl-7-chlorol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and methylamine. 40

' EXAMPLE 87 Using a procedure analogous to that described in Ex-' ample 3, 3-(ethanolamino-methylene)-5-phenyl-7- chloro-l,3-dihydro-2H-l,4-benzodiazepin-2-one, mp. 228230C, of the formula v N-- s0 /=CH-NH-CH -CH OH C -====N was prepared from 3-(dimethylamino-methylene)-5- phenyl-7-chloro-l ,3-dihydro-2H- l ,4-benzodiazepin- 2-one and ethanol-amine.

EXAMPLE 88 Using a procedure analogous to that described in Example 3, l-methyl-3-(ethanolamino-methylene)-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, an amorphous foam (proof of structure by IR-, UV- and NMR-spectra), was prepared from l-methyl- 3-(dimethylamino-methylene)-5-phenyl-7-chloro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and ethanolamine.

EXAMPLE 89 Using a procedure analogous to that described in Example 3, l-methyl-3-[N-(B-diethylamino-ethyl)- amino-methylene ]-5-phenyl-7-chlorol ,3-dihydro-2H- 1,4-benzodiazepin-2-one, an amorphous foam, of the formula 3 I N- c\ y O (proof of structure by IR-, UV- and NMR-spectra) was prepared from l-methyl-3-( dimethylaminomethylene)-5-phenyl-7-chlorol ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and N-(B-diethylamino-ethyl)- amine.

EXAMPLE 90 Using a procedure analogous to that described in Example 3, l-methyl-3 (n-butylamino-methylene)-5- phenyl-7-chloro-1,3-dihydro-2H-l,4-benzodiazepin- 2-one, an amorphous foam (proof of structure by IR-, UV- and NMR-spectra), was prepared from l-methyl- 3-(dimethylamino-methylene)-5-phenyl-7-chloro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and n-butylamine.

EXAMPLE 91 Using a procedure analogous to that described in Example 3, 3-(ethylamino-methylene)-5-(2'-fluorophenyl)-7-nitrol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 240-24lC, was prepared from 3- (dimethylamino-methylene)-5-(2'-fluoro-phenyl)-7- nitrol ,3-dihydro-2H-l ,4-benzodiazepin-2-one and ethylamine.

EXAMPLE 92 Using a procedure analogous to that described in Example 3, l-methyl-3-(ethylamino-methylene)-5-(2- fluoro-phenyl )-7-nitrol ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. l-l 765C. was prepared from l-methyl-3-( dimethylamino-methylene )-5 2 fluoro-phenyl )-7-nitrol ,3-dihydro-2H- l ,4- benzodiazepin-Z-one and ethylamine.

EXAMPLE 93 Using a procedure analogous to that described in Example 3, 3-(amino-methylene)-5-(2'-chloro-phenyl)-7- chloro-l ,3-dihydr0-2H-l ,4-benzodiazepin-2-one, m.p. 220222C, was prepared from 3-(dimethylaminomethylene)-5-( 2 '-chloro-phenyl )-7-chloro-l ,3- dihydro-ZH-l,4-benzodiazepin-2-one and ammonia.

EXAMPLE 94 Using a procedure analogous to that described in Example 3, l-methyl-3-(amino-methylene)-5-(2-chlorophenyl)-7-chlorol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 2()l-204C, was prepared from l-methyl- (3-dimethylamino-methylene)-5-(2'-chloro-phenyl)-7- chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and ammonia.

EXAMPLE 95 Using a procedure analogous to that described in Example 3, 3-(methylamino-methylene)-5-(2'-chl0rophenyl)' 7-chloro-l ,3-dihydr-2H-l ,4-benzodiazepin-2-one, m.p. 225C was prepared from 3-(dimethylaminomethylene )-5-( 2'-chloro-phenyl-7-chloro-l ,3-dihydro- ZH-l ,4-benzodiazepin-2-one and methylamine.

EXAMPLE 96 Using a procedure analogous to that described in Example 3, l-methyl-3-(ethylamino-methylene)-5-(2- chloro-phenyl)- 7-chloro-l ,3-dihydro-2l-l-l ,4-benzodiazepin-2-one, mp. 122C, was prepared from l-methyl-3- (dimethylamino-methylene)- 5-(2-chloro-phenyl)-7-ch1orol ,3-dihydro-2H-l ,4- benzodiazepin-2-one and ethylamine.

EXAMPLE 97 Using a procedure analogous to that described in Example 3, 3-(n-propylamino-methylene)-5-(2'-chlorophenyl)- 7-chloro-1 ,3-dihydro-2H-l ,4-benzodiazepin-2-one, mp. 186C, was prepared from 3-(dimethylaminomethylene)-5-( 2'-chloro-phenyl)-7-chloro-l ,3- dihydro-2H-l ,4-benzodiazepin-2-one and propylamine.

EXAMPLE 98 Using a procedure analogous to that described in Example 3, l-methyl-3-(n-propylamino-methylene)-5- (2'-chloro-phcnyl)- 7-chlorol ,3-dihydro-2H-l ,4-bcnzodiazcpin-2-one, m.p. l46l47C, was prepared from l-methyl-3- (dimethylamino-methylene)- 5-(2'-chloro-phenyl)-7-chloro-l ,3-dihydro-2H- l ,4- benzodiazepin-Z-one and n-propylamine.

EXAMPLE 9'9 Using a procedure analogous to that described in Example 3, 3(isopropylamino-methylene)-5-(2'-chlorophenyl) -7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. l88-l91C, was prepared from 3- (dimethylamino-methylene)-5-(2'-chloro-phenyl)- 7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and isopropylamine.

EXAMPLE l00 Using a procedure analogous to that described in Example 3, 3-(n-butylamino-methylene)-5-(2'-chlorophenyl)- 7-chlorol ,3-dihydro-2H-l ,4-benzodiazepin-2-one, mp. 173C, was prepared from 3-(dimethylaminomethylene )-5-( 2-chloro-phenyl)-7-chloro-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-one and butylamine.

EXAMPLE 10l Using a procedure analogous to that described in Example 3, l-methyl-3-(n-butylamino-methylene)-5-(2- chloro-phenyl )-7-chlorol ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. ll0l 13C, was prepared from l-methyl-3-(diimethylamino-methylene 5-(2'-chloro-phenyl)-7-chlor0- l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and n-butylamine.

EXAMPLE 102 Using a procedure analogous to that described in Example 3, 3-(tert.butylamino-methylene)-5-(2'-chlorophenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, mp. 230C, was prepared from (dimethylamino-methylene)-5-(2chloro-phenyl)-7- chloro-l ,3-dihydro-2H- l ,4-benzodiazepin-2-one and tert.butylamine.

EXAMPLE I03 Using a procedure analogous to that described in Example 3, l-methyl-3 (tert.butylamino-methylene)-5- (2'-chloro-phenyl )-7-chloro-l ,3-dihydro-2l-l-l ,4- benzodiazepin-Z-one, m.p. l-l77C, was prepared from chloro-phenyl)-7-chloro-l ,3-dihydro- 2l-l-l ,4-benzodiazepin-2-one and tert.butylamine.

EXAMPLE 104 Using a procedure analogous to that described in Example 3, 3-(ethanolamino-methylene)-5-(2'-chlorophenyl)- 7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one m.p. 231233C, was prepared from 3- (dimethylamino-methylene)-5-(2'-chlorophenyl)-7- chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and ethanolamine.

EXAMPLE 105 Using a procedure analogous to that described in Example 3, l-mcthyl-3-(ethanolamino-methylene)-5-(2'- chlorophenyl)-7-chlorol ,3-dihydro-2H-l ,4- bcnzodiazcpin-Z-onc, m.p. l55-l57C, was prepared from l-methyl-3 (dimethylaminomcthylenc)5-(2 chloro-phenyl)-7-chloro-l ,Il-dihydro-ZH-l ,4- benzodiazepin-Z-one and ethanolamine.

EXAMPLE 106 Using a procedure analogous to that described in Example 3, 3-[N-(B diethylamino-ethyl)-aminomethylene]-5-(2 -chloro-phenyl)-7-chlorol ,3- dihydro-ZH-l,4-benzodiazepin-2-one, an amorphous foam (proof of structure by IR-, UV- and NMR- spectra), was prepared from 3-(dimethylaminomethylene )-5-(2-chloro-phenyl )-7-chloro-l ,3- dihydro-2H-l,4-benzodiazepin-2-one and diethylamino-ethyl)-amine.

EXAMPLE 107 EXAMPLE 108 Using a procedure analogous to that described in Example 3, l-methyl-3-(ethylamino-methylene)-5-(2- fluorophenyl)-7-chlorol ,3-dihydro-2H- l ,4- benzodiazepin-Z-one, m.p. l5l-l54C, was prepared from l-methyl-3-(dimethylamino-methylene )-5-(2- fluoro-phenyl)-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and ethylamine.

1-methyl-3-(dimethyl-amino-methylene)-5-(2- I EXAMPLE 109 Using a procedure analogous to that described in Example 3, l-methyl-3-(amino-methylene)-5-(2'-chlorophenyl)-7-bromol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, an amorphous substance which decomposed slowly between 80 and llC (proof of structure by IR-, UV- and NMR-spectra), m.p. l86l89.5C (decomp. recrystallized from ether), was prepared from l-methyl-3-(dimethylamino-methylcne)-5-(2'-chlorophenyl)-7-bromo-l ,3-dihydro-2Hl ,4-benzodiazepin- 2-one and ammonia.

EXAMPLE llO Using a procedure analogous to that described in Example 3, l-methyl-3-(ethylamino-methylene )--(2- chlorophenyl )-7-bromo-l ,3-dihydro-2H- l ,4- benzodiazepin-Z-one, m.p. l73l75C, was prepared from 1-methyl-3-( dimethylamino-methylene )-5-( 2 chloro-phenyl )-7-bromol ,3-dihydro-2H-l ,4-benzodiazepin2-one and ethylamine.

EXAMPLE 1 l 1 Using a procedure analogous to that described in Example 3, l-methyl-3-(n-butylamino-methylene)-5-(2'- chlorophenyl )-7-bromo-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l42-l45C, was prepared from 1-methyl-3-(dimethylamino-methylene )-5-( 2 chloro-phenyl )-7-bromo-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one and n-butylamine.

EXAMPLE l 12 Using a procedure analogous to that described in Example 3, l-methyl-3-(cyclopropylamino-methylene)-5- (2-chloro-phenyl )-7-bromol ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 136138C (decomp.), of the formula cams-Q Br mm was prepared from 1-methyl-3-(dimethylaminomethylene )-5-( 2' chloro-phenyl )-7-bromo-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-one and propylamine.

cyclo- EXAMPLE ll3 Using a procedure analogous to that described in Examle 3, lmethyl-3-[N-(ethoxycarbonyl-methyl)- amino-methylene]-5-( 2'-chloro-phenyl)-7-bromo-l ,3-

dihyd ro-2H-l ,4-benzodiazepin-2-one, m.p. l75-l77C, of the formula Br ===-N was prepared from l-methyl-3-(dimethylaminomethylene)-5-( 2'-chloro-phenyl)7-bromo-l ,3- dihydro-ZH-l ,4-benzodiazepin-2-onc and glycine ethyl ester.

EXAMPLE 114 Using a procedure analogous to that described in Example 3, l-mcthyl-3-[(a-furfuryl-amino)-methylenel- 5-(2'-chloro-phenyl)-7-bromol ,3-dihydro-2H- l ,4-

methylene )-5-(2 '-chloro-phenyl)-7-bromol ,3- dihydro-Zl-l-l,4-benzodiazepin-2-one and a-fufurylamine.

EXAMPLE 115 Using a procedure analogous to that described in Example 3, 3-(ethylamino-methylene)-5-(2'-chlorophenyl )-7-nitrol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 26026lC, was prepared from 3 (dimethylamino-methylene)-5-(2-chlorophenyl)-7- nitro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and ethylamine.

EXAMPLE 116 Using a procedure analogous to that described in Example 3, 3-(n-butylamino-methylene)-5-(2'-chlorophenyl)-7-nitro-l,3-dihydro-2H-1,4-benzodiazepin- 2-one, m.p. 222-224C, was prepared from 3- (dimethylamino-methylene)-5-(2-chloro-phenyl)-7- nitro-l,3-dihydro-2H-l,4-benzodiazepin-2-one and nbutylamine.

EXAMPLE 1 17 Using aprocedure analogous to that described in Example 3, 3-[N-(B-diethylamino-ethyl)-aminomethylene]-5-(2'-chloro-phenyl)-7-nitro-l ,3-dihydro- 2H-l,4-benzodiazepin-2-one, m.p. l64-l65C. was prepared from 3-(dimethylaminomethylene)-5-(2- chloro-phenyl)-7-nitro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one and N-(B-diethylamino-ethyl)- amine.

EXAMPLE l 18 Using a procedure analogous to that described in Example 4, l-(B-dimethylamino-ethyl)-3-pyrrolidinomethylene )-5-phenyl-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l39l4 lC, of the formula was prepared from 3-(pyrrolidino-methylene)-5- phenyl-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and B-dimethylaminoethyl chloride.

EXAMPLE 1 19 Using a procedure analogous to that described in Example 4, l-(B-dimethylamino-ethyl)-3- (dimethylamino-methylene)--(2'-chloro-phenyl)-7- chloro-l,3-dihydro-2H-1,4-benzodiazepin-2-one, an amorphous foam (proof of structure by lR-, UV- and NMR-spectra), was prepared from 3-(dimethylaminomethylene )-5 2'-chlorophenyl)-7-chlorol ,3- dihydro-2Hl,4-benzodiazepin-2-one and B-dimethylamino-ethyl chloride.

EXAMPLE 120 Using a procedure analogous to that described in Example 4, l-(cyclopropyl-methyl)-3-(dimethylaminomethylene )-5-( 2-chloro-phenyl)-7-chloro-1 ,3 dihydro-2H-l ,4-benzodiazepin-2-one, m.p. l88190C, was prepared from 3-(dimethylaminomethylene )-5-(2"chloro-phenyl)-7-chloro-l ,3- dihydro-ZH- l ,4-benzodiazepin-2-one and cyclopropylmethyl chloride.

EXAMPLE 121 Using a procedure analogous to that described in Example 4, l-methyl-3-(diethylamino-methylene )-5-(2'- chlorophenyl)-7-chloro-l ,3-dihydro-2H-l ,4-

benzodiazepin-2-one, m.p. 135l37C, was prepared from 3-(diethylamino-methylene)-5-(2'-chlorophenyl )-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and methyl iodide.

EXAMPLE 122 EXAMPLE 124 Using a procedure analogous to that described in Example 4, l-methyl-3-(diisopropylamino-methylene)-5- (2 '-chl0ro-phenyl)-7chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 147149C, was prepared from 3-(diisopropylaminomethylene)-5-(2-chlorophenyl)-7-ehloro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and methyl iodide.

EXAMPLE 125 Using a procedure analogous to that described in Example 4, 1-methyl-3-(di-n-butylamino-methylene)-5- (2 '-chloro-phenyl )-7-chloro-l ,3-dihydro-2H- l ,4 benzodia2epin-2-one, an amorphous foam (proof of structure by IR-, UV- and NMR- spectra), was prepared from 3-(n-butylamino-methylene)-5-(2 -chloropheny1)-7-chloro-l ,3-dihydro-2H-l ,4-benzodiazepin 2-one and methyl iodide.

EXAMPLE 126 Using a procedure analogous to that described in Example 4, l-methyl-3-[(N-cyelohexyl-N-methyl-amino)- methylene]-5-(2-chloro-phenyl)-7-chlorol ,3- dihydro-2H-1,4-benzodiazepin-2-one, m.p. ll72C, was prepared from 3-[(N-cyclohexyl-N- methyl-amino)-methylene]-5-(2'-chloro-phenyl)-7- chloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and methyl iodide.

EXAMPLE 127 Using a procedure analogous to that described in Example 4, l-methyl-3-(pyrrolidino-methylene)-5-(2'- chlorophenyl)-7-chlorol ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 18l-183C, was prepared from 3-(pyrrolidinomethylene)-5-(2-chloro-phenyl)- 7-ehloro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and methyl iodide.

EXAMPLE 12s Using a procedure analogous to that described in Example 4, l-methyl-3-(piperidino-methylene)-5-(2- ehlorophenyl)-7-chloro-1,3-dihydro-2H-1,4- benzodiazepin-Z-one, an amorphous foam (proof of structure by IR-, UV- and NMR-spectra), was prepared from 3-(piperidino-methylene)-5-(2'-ehlorophenyl)-7- ehloro-l ,3-dihyd'ro-2H-l ,4-benzodiazepin-2-one and methyl iodide.

EXAMPLE 129 Using a procedure analogous to that described in Example 4, l-methyl-3-( hexamethyleneiminomethylene)-5-(2-chloro-phenyl)-7-chloro-l ,3- dihydro-ZH-l ,4 -benzodiazepin-2-one, an amorphous foam (proof of structure by IR, UV- and spectra), was prepared from 3-(hexamethyleneimino-methylene)-5- (2'-chloro-phenyl)-7-chloro-l ,3 -dihydro-2H-l ,4- benzodiazepin-2-one and methyl iodide.

EXAMPLE 130 Using a procedure analogous to that described in Example 4, 1-methyl-3-(morpholino-methylene)-5-(2- chlorophenyl )-7-chloro-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 153-155C, was prepared from 3-(morpholino-methylene)-5-(2'-chloro-phenyl)- 7-chloro-l,3-dihydro-2H-1,4-benzodiazepin-2-one and methyl iodide.

EXAMPLE 131 Using a procedure analogous to that described in Example 4, l-methyl-3-(dimethylamino-methylene)-5- (2'-chlorophenyl)-7-bromo-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l98-l99C, was prepared from 3-(dimethylamino-methylene)-5-(2-chlorophenyl)-7-bromo-l ,3-dihydro-2H-1,4-benzodiazepin- 2-one and methyl iodide.

EXAMPLE 132 Using a procedure analogous to that described in Example 4, l-methyl-3-(ethylamino-methylene)-5-(2- chlorophenyl )-7-nitro-l ,3-dihydro-2l-l- 1 ,4- benzodiazepin-Z-one, m.p. l59l61C, was prepared from 3-(ethylamino-methylene)-5-(2'-chloro-phenyl)- 7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and methyl iodide.

EXAMPLE 133 Using a procedure analogous to that described in Example 4, 1-methyl-3-(n-buty[amino-methylene)-5-(2'- chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4 benzodiazepin-2-onc, m.p. 90C (decomp.), was prepared from 3-(n-butylamino-mcthylcnc)-5-(2'-chlorophcnyl)-7-nitro-l,3-dihydro-2H-1,4-bcnzodiazepin- 2-one and methyl iodide.

EXAMPLE 134 Using a procedure analogous to that described in Example 4, 1-methyl-3'(dimethylamino-methylene)-5- (2-chlorophenyl)-7-nitro-l,3-dihydro-2H-1,4- benzodiazepin-Z-one, m.p. l82-l83C, was prepared from 3-(dimethylamino-methylene)-5-(2'-chlorophenyl)-7-nitro-l ,3-dihydro-2H- l ,4-benzodiazepin- 2-one and methyl iodide.

EXAMPLE 135 Using a procedure analogous to that described in Example 4, 1-(B-dimethylaminoethyl)-3-(diethylaminomethylene )-5 2'-chloro-phenyl)-7-nitro-1 ,3-dihydro- ZH-l ,4-benzodiazepin-2-one, m.p. 103C, was prepared from 3-(diethylamino-methylene)-5-(2'-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepin- 2-one and B-dimethy1amino-ethyl chloride.

EXAMPLE 136 Using a procedure analogous to that described in Example 4, 1-(B-dimethylamino-ethyl)-3-(pyrro1idinomethylene )-5-( 2-chloro-phenyl )-7-nitro-1 ,3-dihydro- 2H-l,4-benzodiazepin-2-one, m.p. 209210C, was prepared from 3-(pyrrolidinomethylene)-S-(2-chlorophenyl)-7-nitro-1,3-dihydro-2H-1 ,4-benzodiazepin- 2-one and 62-dimethy1amino-ethyll chloride.

EXAMPLE 137 Using a procedure analogous to that described in Example 4, 1methyl-3-(piperidino-methylene)-5-(2- chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4- benzodiazepin-2-one, m.p. 13914lC, was prepared from 3-(piperidino-methylene)-5-(2-chloro-phenyl)- 7-nitro-1 ,3-dihydro-2l-l-1,4-benzodiaZepin-2-one and methyl iodide.

EXAMPLE l3 8 Using a procedure analogous to that described in Example 4, 1-(B-dimethylamino-ethyl)-3-piperidinomethylenc)-5-(2-chloro-phenyl)-7-nitro-1,3-dihydro- 211-1,4-benzodiazepin-2-one, m.p. 103106C, was prepared from 3-(piperidinomethylene)-5-(2'-chlorophenyl)-7-nitro-l ,3-dihydro-2H-l ,4-benzodiazepin- 2-one and B-dimethylamino-ethyl chloride.

EXAMPLE 139 Using a procedure analogous to that described in Example 4, 1 -methyl-3-( hexamethyleneiminomethylene )-5-( 2'-ch1oro-phenyl )-7-nitro- 1 ,3-dihydro- 2H-1,4benzodiazepin-2-one, m.p. 98-105C, was prepared from 3-(hexamethyleneiminomethylene)5-(2'- chloro-phenyl)-7-nitro-l,3-dihydro-2H-1,4- henzodiazepin-Z-one and methyl iodide.

EXAMPLE 140 Using a procedure analogous to that described in Example 4, l-methyl-3-(morpholino-methylene)-5-(2- ch1orophenyl)-7-nitr0-1,3-dihydro-2H-l,4-

benzodiazcpin-Z-onc, m.p. 102-105C, was prepared from 3-(morpholino-methylene)-5-(2'-chloro-phenyl% 7-nitro-1,3-dihydro-2H-1,4-bcnzodiazcpin-2-onc and methyl iodide.

EXAMPLE 141 EXAMPLE 142 Using a procedure analogous to that described in Example 141, 3-( dimethylamino-methylene )-5-( 2 chloro-phenyl )-7-fluoro-1 ,3-dihydro-2H-l ,4- benzodiazepin-2-one, m.p. 210-21 1C, of the formula was prepared from 5-(2-chloro-phenyl)-7-fluoro-1,3- dihydro-ZH-l ,4-benzodiazepin-2-one and MN- dimethyl-formamide-diethylacetal.

EXAMPLE 143 Using a procedure analogous to that described in Example 141 3-(morpholino-methylene)-5-( 2'-chlorophenyl)-7-fluoro-1,3-dihydro-2H-l ,4-benzodiazepin- 2-one, m.p. 243-246C (decomp.), was prepared from 5-(2-chloro-phenyl)-7-fluoro1 ,3-dihydro-2H1,4- benzodiazepin-2-one and morpholino-diethoxymethane.

EXAMPLE 144 Using a procedure analogous to that described in Example 141, 3-(dimethylamino-methylene )-5-( 2 chloro-phenyl)-7-iodo-l ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. 227-230C, of the formula was prepared from -(2i-chloro-phenyl)-7-iodo-l,3- dihydro-2H-l ,4-benzodiazepin-2-one and N ,N- dimethyl-formamide-diethylacetal.

EXAMPLE 145 5 Using a procedure analogous to that described in EX- ample 141, 3-(morpholino-methylene)-5-(2-chlorophenyl)-7-iodol ,3-dihydro-2H-l ,4-benzodiazepin- 2-one, mp. 218.5221C, was prepared from 5-(2'- chloro'phenyl)-7-iodo-l ,B-dihydro-ZH-l ,4- benzodiazepin-2-one and morpholino-diethoxymethane.

EXAMPLE 147 Using a procedure analogous to that described in Example l46, l-ethyl-3-(diethylamino-methylene)-5-(2'- chlorophenyl)-7-chloro-l ,3-dihydro-2l-l-l ,4- benzodiazepin-2-one, an oily substance, of the formula was prepared from l-ethyl-5-(2-chloro-phenyl)-7- chloro-1,3-dihydro-2H-l,4-benzodiazepin-2-one and N,N-diethyl-formamiciediethylacetal. lR-spectrum in methylene chloride:

2960 cm 2940 cm"} CH2, CH;, 2570 cm 1635 cm lactam C 0 I575 cm" C C. C N I600 cm EXAMPLE 148 Using a procedure analogous to that described in Example 146, l-( 2,2',2'-trifluoro-ethy l)-3- (dimethylamino-methylene)-5-(2"-chloro-phenyl)-7- bromo-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one, m.p. 2l62l7C, of the formula F3C=ClIH2 o CH B}? m was prepared from l-(2',2',2'-trifluoro-ethyl)-5-(2"- chloro-phenyl)-7-bromol ,S-dihydro-ZH- l ,4- benzodiazepin-2-one and N,N-dimethyl-formamidediethylacetal.

EXAMPLE 149 Using a procedure analogous to that described in Example 146, l-methyl-3-(morpholino-methylene)-5-(2- chloro-phenyl)-7-iodo-1,3-dihydro-2Hl-l,4- benzodiazepin-Z-one, m.p. l93l95C, was prepared from dihydro-2H-l ,4-benzodiazcpin-2-one and morpholinodiethoxy-mcthane.

EXAMPLE l 50 3-(Amino-methylene)-7-chloro-5-(2'-fluoro-phenyl)- l,3-dihydro-2H-l,4-benzodiazepin-2-one by method B Dry, gaseous ammonia was passed for four hours into a solution of 9 gm of 7-chloro-l ,3-dihydro'3- (dimethylamino-methylene)- 5-(2'-fluoro-phenyl)-2H- 1,4-benzodiazepin-2-one and a spatulatipful of ammonium chloride in ml of dimethylformamide at C, accompanied by stirring. Thereafter, the reaction solution was evaporated to dryness in vacuo, and the yellowish-brown residue was crystallized from isopropanol/petroleum ether, yielding the compound named in the heading, which had a melting point of 275-280C.

EXAMPLE l5l 7-Chloro-5-(2 '-chloro-phenyl)-l ,3-dihydr0- 1 -methyl- 3-(thio-morpholino-methylcne )-2l-ll ,4-benzodiaze- .pin-Z-onc-S-oxidc by method B 5.4 gm of thiomorpholinc-S-oxidc were added to a solution of 11.2 gm of 7-chloro-5-(2'-chloro-phenyl)- l,3-dihydro-3-(dimcthylamino-methylene )-l methyl- 2H-l ,4-benzodiazepin-2-one in 70 ml of dimethylformamide, and the mixture was heated at l40C for 24 hours. Therefore, the reaction solution was evaporated to dryness in vacuo, and the yellowish-brown residue was crystallized from isopropanol, yielding the compound of the formula which had a melting point of ll9lC (decomp.).

EXAMPLE 152 Using a procedure analogous to that described in Example 150, 3-(amino-methylene)-5-( 2'-chlorophenyl)-7-fluoro-l ,3-dihydro-2H- l ,4-benzodiazepin- 2-one, m.p. l73l74C, was prepared from 3- (dimethylamino-methylene)-5-(2'-chloro-phenyl))-7- fluoro-l ,3-dihydro-2H- l ,4-benzodiazepin-2-one and ammonia.

l-methyl-5-( 2 '-chloro-phenyl )-7-iodo-l ,3-

EXAMPLE 153 Using a procedure analogous to that described in Example 150, 1-methyl-3-(amino-methylene)-5-(2'- chloro-phenyl)-7-flu0ro-1,3-dihydro-2H-1,4- benzodiazepin-2-one, m.p. 105-110C, was prepared from 1-methyl-3-(dimethylamino-methylene )-5-( 2'- ch1oro-phenyl)-7-fluoro-1,3-dihydro-2H-1,4- benzodiazepin-Z-one and ammonia.

EXAMPLE 154 Using a procedure analogous to that described in EX- ample 150, 3(ethylamino-methylene)-5-(2-chlorophenyl)-7-fluoro-1,3-dihydro-2H-1,4-benzodiazepin- 2-one, m.p. 138-141C, was prepared from 3- (d1methylamino-methylene)-5-(2'chloro-phenyl)-7- fluoro-l,3-dihydro-2H-1,4-benzodiazepin-2-one and ethylamine.

EXAMPLE 155 Using a procedure analogous to that described in Example 150, B-(ethylamino-methylene)--(2-ch1orophenyl)- 7-fluoro-1,3-dihydro-2H-l,4-benzodiazepin- 2-one, m.p. 138-14lC, was prepared from 3- (dimethylamino-methylene)-5-(2'-chloro-phenyl)-7- fluoro-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one and ethylamine.

EXAMPLE 156 EXAMPLE 157 Using a procedure analogous to that described in EX- ample 150, 1-methyl-3-(methylamino-methylene)-5- (2-chlorophenyl)-7-chloro-1,3-dihydro-2H-1,4- benzodiazepin-Zone, m.p. 155158C, was prepared from 1methy1-3-( dimethylamino-methylene)-5-( 2'- chloro-phenyl)-7-chloro-1,3-dihydro-2H-1,4- benzodiazepin-Z-one and methylamine.

EXAMPLE 158 Using a procedure analogous to that described in EX- ample 141, 1-methyl-3-(thiomorpholine-methylene)-5- (2'-chloro-phenyl)-7-chloro-1,3-dihydro-2H-l,4- benzodiazepin-Z-one, a foamy solid, was prepared from 1-methy1-5-( 2-ch1oro-phenyl)7'chloro-l ,B-dihydro- 2H-1,4-bcnZodiaZepin-2-one and thiomorpholinodiethoxy-methane. lR-spectrum in methylene chloride:

2800 cm" N-alkyl 1650 cm lactam-CO 1600 cm" C C 1575 cm 1 C N 1500 cm" EXAMPLE 159 Using a procedure analogous to that described in EX- ample l50,3-(amino-methylene)-5-(2-chlorophenyl)-7-bromo-1,3-dihydro-2H-l,4-benzodiazepin- 2-one, m p. 2 1 6 2 1 8C (decomp.), was prepared from 3-(dimethylamino-methylene)-(2 chl6"o phenm 7- bromo-l,3-dihydro-2H-1,4-benzodiazepin-2-one and ammonia.

EXAMPLE 160 Using a procedure analogous to that described in EX- ample 150, 1-methyl-3-(methylamino-methylene)-5- (2'-chloro-phenyl)-7-bromo-1,3-dihydro-2l-l-1,4- benzodiazepin-2-one, m.p. 1571S8C, was prepared from 1-methyl-3-(dimethylaminn-methylene)-5-( 2- ch1oro-phcnyl)-7-bromol ,3-dihydro-2H-1 ,4- benzodiazepin-Z-one and methylamine.

EXAMPLE 161 Using a procedure analogous to that described in EX- ample 150, 3-(ethy1amino-metl1ylene)-5-(2-chlorophenyl)7-bromo-l,3-dihydro-2H-1,4-benzodiazepin- Z-one, m.p. 227229C, was prepared from 3- (dimethylamino-methylene)-5-(2'-ch1oro-phenyl-7- bromo-l ,3-dihydro-2l-l-1,4-benzodiazepin-2-one and ethylamine.

EXAMPLE 162 Using a procedure analogous to that described in Example 150, 3-(amino-methy1ene)'5-( 2'-ch1orophenyl)-7-iodo-1,3-dihydro-2H-1,4-benzodiazepin- 2-one, m.p. l67172C (decomp.), was prepared from 3-(dimethylamino-methylene)-5-(2-chloro-phenyl)-7- iodol ,3-dihydro-2H- l ,4-benzodiazepin'2-one and ammonia.

EXAMPLE 163 Using a procedure analogous to that described in Example 150, 1-methyl-3-(amino-methylene)-5-(2- chloro-phenyl)-7-iodo-1,3-dihydro-2H-1,4- benzodiazepin-2-one, m.p. 130C (decomp.), was prepared from l-methy1-3-(dimethylamino-methylene)-5- (2-chloro-phenyl)-7-iodo- 1 ,3-dihydro- 2 H- 1 ,4-beiiz6- diazepin-Z-one and ammonia.

EXAMPLE 164 Using a procedure analogous to that described in EX- ample 150, 3-(ethylamino-methylene)-5-(2'-chlorophenyl)-7-iodo-1,3-dihydro-2H-1,4-benzodiazepin- 2-one, m.p. 212214C, was prepared from 3- (dimethylamino-methylene)-5-(2'-chloro-phenyl)-7- iodo-l ,3-dihydro-2H-1,4-benzodiazepin-2-one and eth ylamine.

EXAMPLE 165 Using a procedure analogous to that described in EX- ample 150, 1-methyl-3-(ethylamino-methylene)-5-(2'- chlorophenyl)-7-iodo-l,3-dihydro-2H-1,4- benzodiazepin-Z-one, m.p. 202206C, was prepared from 1-methyl-3-(dimethlamino-methylene)-5-(2'- chloro-phenyl)-7-iodo1 ,3-dihydro-2H-1,4- benzodiazepin-Z-one and ethylamine.

EXAMPLE 166 Using a procedure analogous to that described in Example 150, l-methyl-3(amino-methylene)-5-(2'- chloro-phenyl)-7-nitro-l ,3-dihydro-2H-, 1,4- benzodiazepin-Z-one, m.p. l40l43C (decomp.), was prepared from 1-methyl-3-(dimethylaminomethylene 2'-chloro-Phenyl)-7-nitro-1 ,S-dihydro- 21-1-1,4-benzodiazepin2-one and ammonia.

EXAMPLE 167 5-( 2-Chloro-phenyl)- l ,3-dihydro-7-fluoro- 1 -methyl- 3-(morpholino-methylene)2H-1,4-benzodiazepin- 2-one by method C 1.6 gm of a methanolic 30% sodium methylate solution were added to a suspension of 2 gm of 5-(2'- chlorophenyl)-l ,3-dihydro-7-fluoro-3-(morpholinomethylene)2l-l-l ,4-benzodiazepin-2-one in 50 ml of di- EXAMPLE 168 Using a procedure analogous to that described in Example 167, 1-methyl-3-(dimethylamino-methylene-5- (2-ch1oro-phenyl)-7-fluorol ,3-dihydro-2H-l ,4- benzodiazepin-Z-one, m.p. l77179C, was prepared from 3-(dimethylamino-methylene)-5-(2-chlorophenyl)-7-fluoro-1,3-dihydro-2H-l ,4-benzodiazepin- 2-one, sodium methylate and methyl iodide.

The compounds of the present invention, that is, those embraced by formula 1 above, have useful pharmacodynamic properties. More particularly, they exhibit sedative, tranquilizing, muscle-relaxing and anticonvulsive activities in warm-blooded animals, such as mice.

The muscle-relaxing, sedative and anticonvulsive activities of the compounds of the present invention were ascertained by standard pharmacological test methods. The results of these tests for certain selected compounds, which are representative and illustrative of the genus, are shown below, where A 7-Chloro-5-(2-chloro-phenyl)l,3-dihydro-lmethyl-3-( morpholino-methylene )-2H-l ,4- benzodiaZepin-2'one,

B 3- (Amino-methylene)-7-chloro-5-(2-chlorophenyl )-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one, 3-(Ethylamino-methylene)7-chloro-5-(2'- chloro-phenyl)-l ,3-dihydrol -methyl-2H- l ,4- benzodiazepin-Zone,

7Bromo-5-( 2 '-chloro-phenyl )-l ,3-dihydrol methyl-3-( morpholino-methylene )-2H-l ,4 benzodiazepin-Lone,

3-(Amino-methylene)-7-bromo-5-(2-chlorophenyl )-1 ,3-dihydro- 1 -methyl-2H- l ,4- benzodiazepin-2-one, F 3-(Amino-methylene)-7-bromo-5-(2-chlorophenyl)-l,3-dihydro-2H-1,4-benzodiazepin-2-one, 3-(Ethylamino-methylene)-7-bromo-5-(2'- chloro-phenyl)-l ,3-dihydro-2H-l ,4- bcnzodiazepin-Z-one and H 3-(Amino-methylene)-5-(2-chloro-phenyl)-l ,3- dihydro-7-iodo-l -methyl-2H- l ,4benzodiazepin- 2-one.

1. Muscle-relaxing and sedative activity The muscle-relaxing and sedative activites are tested by the method of Young and Lewis [Science 105, 368 (1947)] on female NMRl-mice of our own breed with a body weight between 20 and 26 gm by means of slowly turning wire-mesh cylinders, inclined at 30from the vertical (length 43 cm; diameter 22 cm; meshsize of the wire netting: 0.6 cm). After peroral administration of the test compound in the form of a 1% suspension in tylose to groups of 10 mice/dose their holding ability in the slowly rotating cylinders was tested (2rotations/minute) against a control group. The median effective dose (ED was graphically determined which caused 50% of the animals to fall out of the cylinders at various time intervals after administration.

TABLE I Com- ED mgm/kg p.o pound after 30- after after 210- after 270- 60 min. min. 240 min. 300 min.

A 14 5 14 3 B 13 3 10 l I C 2 3 l 1 3 D 33 2o lo 13 E 7 7 5 6 F 0.5 0.7 0.7 1.9 G 2.4 1.25 2.1 2.4

2. Anticonvulsive activity The anticonvulsive activity was tested in terms of the protective effect against the maximum electro-shockspasm in male NMRlmice of our own breed with a body weight between 20 and 26 gm analogous to Swinyard, Brown and Goodman [.l. Pharmacol. exp, Therap, 106, 319 (1952)]. The animals were exposed to an alternating current of 50 cycles and 50 milliamperes (duration of stimulation 0.2 seconds), where the occurrence of the tonic extensor spasm was valued as positive. After peroral administration of the test compound in the form of a 1% suspension in tylose, the dose (ED was graphically determined which protected 50% of the animals against the tonic extensor component of the back extremities after various time intervals.

3. Effect on spontaneous motility TABLE 111 Compound ED mgm/kg p.o.

after 90-95 min. after 150-155 min.

D 4.4 5.2 F 8.15 3.76 G 1 l .56 2.45

It should be added that the compounds of the instant invention are virtually non-toxic. For instance, by standard acute toxicity tests we determined that even massive doses of 6 400 mgm/kg p.o. of compound A or 3 200 mgm/kg p.o. of compounds B or C produced no deaths in a group of 10 adult laboratory mice within 14 days.

For pharmaceutical purposes the compounds according to the present invention are administered to warmblooded animals perorally or parenterally as active ingredients in customary dosage unit compositions, that is, compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one effective dosage unit ofthe active ingredient, such as tablets, coated pills, capsules, wafers, powders, suppositories and the like. one effective dosage unit of the compounds according to the present invention is from 0.033 to 0.34 mgm/kg body weight, preferably 0.083 to 0.167 mgm/kg body weight; the daily dose rate is 0.083 to 1.34 mgm/kg body weight, preferably 0.16 to 0.67 mgm/kg body weight.

The following examples illustrate a few pharmaceutical dosage unit compositions comprising a compound of the present invention as an active ingredient and represent the best modes contemplated of putting the invention into practical use. The parts are parts by weight unless otherwise specified. 1

EXAMPLE 169 Tablets The table composition is compounded from the following ingredients:

3-( Ethylamino-methylene)-7-bromo-5-( 2'- chloro-phenyl)-1,3-dihydro-2H-1,4-

benzodiaze pin-2-one 5 parts Lactose 75 Corn starch 37 do. Gelatin 2 do. Magnesium stearate 1 do.

Total 1 parts 1.0 mm-mesh screen, and the dry granulate thus obtained is admixed with the magnesium stearate. The resulting composition is compressed into mgmtablets in a conventional tablet making machine. Each tablet contains 5 mgm of the benzodiazepinone compound and is an oral dosage unit composition with effective sedative, tranquilizing, muscle-relaxing and anticonvulsive action.

EXAMPLE Coated tablets The tablets prepared pursuant to Example 169 are coated with a thin shell consisting essentially of a mixture of sugar and talcum, and the coated tablets are polished with beeswax. The coated tablets contain the same amount of active ingredient and have the same pharmacological effect as the uncoated tablets of Example 169.

EXAMPLE 171 Suppositories The suppository composition is compounded from the following ingredients:

benzodiazepin-Z-one 30 parts Suppository base (e.g. cocoa butter) 1670 do.

Total 1700 parts EXAMPLE 172 Gelatin capsules The capsule filler composition is compounded from the following ingredients:

3-( Ethylamino-methylene )-7-ch10ro-5-(2- chloro-phenyl)-l ,3-dihydro-1 -methy1- 2H-1.4-benzodiazepin-2-one 5 parts Corn starch, dry 174 do. Magnesium stearate 1 do.

Total parts Preparation:

The ingredients are intimately admixed with each other, and 180 mgm-portions of the mixture are filled into size 4 gelatin capsules. Each capsule contains 5 mgm of the benzodiazepinone compound and is an oral dosage unit composition with effective sedative, tranquilizing, muscle-relaxing and anticonvulsive action.

Analogous results were obtained when any one of the other benzodiazepinones embraced by formula 1 was substituted for the particular benzodiazepinonein Examples 170 through 172. Likewise, the amount of active ingredient in these illustrative examples may be varied to achieve the dosage unit range set forth above, and the amounts and nature of the inert pharmaceutical carrier ingredients may be varied to meet particular requirements.

While the present invention has been illustrated with the aid of certain specific embodiments thereof, it will be readily apparent to others skilled in the art that the invention is not limited to these particular embodiments, and that various changes and modifications may be made without departing from the spirit of the invention or the scope of the appended claims.

We claim:

1. A compound of the formula R and R are each hydrogen cycloalkyl of 3 to 6 carbon atoms, phenyl,

attached, pyrrolidino, piperidino, hexamethyleneimino, morpholino, thiomorpholino, thiomorpholino-S-oxide or N '-lower alkyl-piperazino R is halogen nitro or trifluoromethyl,

R is hydrogen, halogen or trifluoromethyl, and

R is hydrogen, lower alkyl, (cycloalkyl of 3 to 6 carbon atoms)-methyl, lower alkyl-arnino-lower alkyl, di(lower alkyl) amino-lower alkyl or trifluoromethyl-lower alkyl.

2. A compound of claim 1, wherein R and R are each hydrogen or alkyl of l to 3 carbon atoms or, together with each other and the nitrogen atom to which they are attached, morpholino or thiomorpholino-S-oxide,

R and R are each halogen, and

R is hydrogen or alkyl of l to 3 carbon atoms.

3. The compound of claim 1 which is 3-(aminomethylene )-7-bromo-5-( 2-chloro-phenyl)-l ,3- dihydrol -methyl-2H- 1 ,4-benzodiazepin-2-one.

4. The compound of claim 1 which is 3-(ethylaminomethylene )-7-chloro-5-( 2'-chloro-phenyl )-1 ,3- dihydro-l-methyl-2H-1,4benzodiazepin-2-one.

5. The compound of claim 1 which is 3-(aminomethylene )-7-chloro-5-( 2-chloro-phenyl)- l ,3- dihydro2H- l ,4-benzodiazepin-2-one.

6. The compound of claim 1 which is 7-bromo-5-(2- chloro-phenyl)- 1 ,3-dihydro-l -methyl-3-( morpholinomethylene )-2Hl ,4-benzodiazepin-2-one.

7. The compound of claim 1 which is 7-chl'oro-5-(2- chloro-phenyl)-l ,3-dihydrol -methyl-3- morpholinomethylene)-2H-l ,4-benZ0diazepin-2-one.

8. The compound of claim 1 which is. 3- (aminomethylene)-7-bromo-5-(2'-chloro-phenyl)-1,3- dihydro-ZH-l ,4-benzodiazepin-2-one.

9. The compund of claim 1 which is 3- (ethylaminomethylene)-7-bromo-5-(2'-chlorophenyl)-l ,3-dihydro-2H-l ,4-benzodiazepin-2-one.

10. The compound of claim 1 which is 3- (aminomethylene)-5-(2'-chloro-phenyl) -l,3-dihydro- 7-iodol -methyl-2H-l ,4-benzodiazepin-2-one. 

1. A COMPOUND OF THE FORMULA
 2. A compound of claim 1, wherein R1 and R2 are each hydrogen or alkyl of 1 to 3 carbon atoms or, together with each other and the nitrogen atom to which they are attached, morpholino or thiomorpholino-S-oxide, R3 and R4 are each halogen, and R5 is hydrogen or alkyl of 1 to 3 carbon atoms.
 3. The compound of claim 1 which is 3-(amino-methylene)-7-bromo-5-(2''-chloro-phenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one.
 4. The compound of claim 1 which is 3-(ethylamino-methylene)-7-chloro-5-(2''-chloro-phenyl)-1,3-dihydro-1-methyl -2H-1, 4benzodiazepin-2-one.
 5. The compound of claim 1 which is 3-(amino-methylene)-7-chloro-5-(2''-chloro-phenyl)-1,3-dihydro-2H-1,4 -benzodiazepin-2-one.
 6. The compound of claim 1 which is 7-bromo-5-(2''-chloro-phenyl)-1,3-dihydro-1-metHyl-3-(morpholino-methylene) -2H-1,4-benzodiazepin-2-one.
 7. The compound of claim 1 which is 7-chloro-5-(2''-chloro-phenyl)-1,3-dihydro-1-methyl-3-morpholinomethylene)-2H-1,4-benzodiazepin-2-one.
 8. The compound of claim 1 which is 3-(aminomethylene)-7-bromo-5-(2''-chloro-phenyl)-1,3-dihydro-2H-1,4 -benzodiazepin-2-one.
 9. The compund of claim 1 which is 3-(ethylaminomethylene)-7-bromo-5-(2''-chloro-phenyl)-1,3-dihydro-2H-1,4 -benzodiazepin-2-one.
 10. The compound of claim 1 which is 3-(aminomethylene)-5-(2''-chloro-phenyl) -1,3-dihydro-7-iodo-1-methyl-2H-1,4-benzodiazepin-2-one. 